Kowa Pharmaceuticals America, Inc. Announces Appeals Court Decision Upholding Patent Protection for LIVALO® (pitavastatin)

MONTGOMERY, Ala.--(BUSINESS WIRE)-- Kowa Pharmaceuticals AmericaInc. announced today that the U.S. Court of Appeals for the Federal Circuit has affirmed the decision by the U.S. District Court for the Southern District of New York, upholding the validity of U.S. Patent No. 8,557,993 (the ‘993 patent) protecting the Company’s cholesterol-lowering drug LIVALO^® (pitavastatin) tablets. This decision was the most recent in litigation involving challenges by eight generic companies to the patents protecting the statin LIVALO^®. Several of those defendants settled, and the U.S. District Court entered judgment against the two remaining defendants, the generic drug manufacturers Amneal Pharmaceuticals LLP and Apotex, Inc. and Apotex Corp.

“We are pleased with the U.S. Court of Appeals’ ruling upholding the validity of the ‘993 patent for LIVALO^® once again,” said Ben Stakely, Chairman, CEO and President of Kowa Pharmaceuticals America, Inc. “Our focus continues to be centered around bringing LIVALO^® to patients with high cholesterol and the physicians who treat them, as well as continuing to increase awareness and education about the risks of high cholesterol.”

The U.S. District Court issued two decisions – one in April 2017 upholding the validity and infringement of U.S. Patent No. 5,856,336 (the ‘336 patent), and the second in October 2017 upholding the validity and infringement of the ‘993 patent. The ‘336 patent, which expires on December 25, 2020, covers pitavastatin calcium, the active ingredient in LIVALO^®. The ‘993 patent, which expires on February 2, 2024, covers the polymorphic form of pitavastatin calcium in LIVALO^®.

The plaintiffs, which included Kowa Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Corporation, prevailed on all issues in the U.S. District Court decisions. Amneal and Apotex both filed appeals to the U.S. Court of Appeals for the Federal Circuit. Apotex subsequently abandoned its appeal and settled, agreeing to license to market its generic version of LIVALO^® beginning on May 2, 2023, or earlier under certain circumstances. Oral argument on the Amneal appeal was held on December 6, 2018, and the Federal Circuit entered its decision affirming the District Court’s judgment on December 10, 2018. As a result of the Federal Circuit decision, Amneal will be precluded from marketing its generic version of LIVALO^® until after the expiration of the ‘993 patent in February 2024.

Kowa Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Corporation are represented by Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

About LIVALO^®

LIVALO^® is an HMG-CoA reductase inhibitor (statin).

INDICATIONS AND USAGE

Drug therapy should be one component of multiple-risk-factor intervention in individuals who require modifications of their lipid profile. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.

PRIMARY HYPERLIPIDEMIA AND MIXED DYSLIPIDEMIA

LIVALO^® (pitavastatin) is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hyperlipidemia or mixed dyslipidemia.

LIMITATIONS OF USE

• Doses of LIVALO^® greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4-mg, once-daily dosing of LIVALO^®
• The effect of LIVALO^® on cardiovascular morbidity and mortality has not been determined
• LIVALO^® has not been studied in Fredrickson Type I, III, and V dyslipidemias

Important Safety Information for LIVALO^® (pitavastatin) tablets

CONTRAINDICATIONS

LIVALO^® is contraindicated in patients with a known hypersensitivity to product components, in patients with active liver disease (which may include unexplained persistent elevations in hepatic transaminase levels), in women who are pregnant or may become pregnant, in nursing mothers, or in co-administration with cyclosporine.

WARNINGS AND PRECAUTIONS

Skeletal Muscle Effects

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including LIVALO^®. These risks can occur at any dose level, but increase in a dose-dependent manner.

• LIVALO^® should be prescribed with caution in patients with predisposing factors for myopathy.
• The risk of skeletal muscle effects (e.g., myopathy and rhabdomyolysis) increases in a dose-dependent manner with advanced age (≥65 years), renal impairment, inadequately treated hypothyroidism, and in combination use with fibrates or lipid-modifying doses of niacin (≥1 g/day).
• LIVALO^® should be administered with caution in patients with impaired renal function, in elderly patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin.
• Concomitant administration of LIVALO^® with gemfibrozil should be avoided.
• LIVALO^® therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. LIVALO^® therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, and electrolyte disorders; or uncontrolled seizures).
• Advise patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, and to discontinue LIVALO^® if these signs or symptoms appear.
• Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should be exercised when prescribing LIVALO^® with colchicine.
• There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents. IMNM has not been reported with LIVALO therapy.
• Advise patients to promptly report if muscle signs and symptoms persist after discontinuing LIVALO^® as this may be a sign of IMNM requiring immediate medical attention.

Liver Enzyme Abnormalities

Increases in serum transaminases have been reported with HMG-CoA reductase inhibitors, including LIVALO^®.

• It is recommended that liver enzyme tests be performed before the initiation of LIVALO^® and if signs or symptoms of liver injury occur.
• There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with LIVALO^®, promptly interrupt therapy. If an alternate etiology is not found do not restart LIVALO^®.
• Advise patients to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
• LIVALO^® should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease.

Endocrine Function

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIVALO^®.

ADVERSE REACTIONS

In short-term controlled studies, the most frequent adverse reactions reported by ≥2% of patients treated with LIVALO^® 1 mg, 2 mg, and 4 mg, respectively, and at a rate ≥ placebo were back pain (3.9%, 1.8%, 1.4% vs 2.9%), constipation (3.6%, 1.5%, 2.2% vs 1.9%), diarrhea (2.6%, 1.5%, 1.9% vs 1.9%), myalgia (1.9%, 2.8%, 3.1% vs 1.4%), and pain in extremity (2.3%, 0.6%, 0.9% vs 1.9%). This is not a complete listing of all reported adverse events.

For additional information, please see the full Prescribing Information at www.LivaloRx.com.

© Kowa Pharmaceuticals America, Inc. (2016) - LIV-RA-0101 PI V-11-2016

About Kowa Company, Ltd. and Kowa Pharmaceuticals America, Inc.

Kowa Company, Ltd. (Kowa) is a privately held, multinational company headquartered in Nagoya, Japan. Established in 1894, Kowa is actively engaged in various business fields including the trading of textiles, machinery, and construction materials, in addition to the manufacturing and sales of medicines, medical equipment, and energy saving products. Kowa's pharmaceutical division is focused on research and development for cardiovascular therapeutics (dyslipidemia, type 2 diabetes and atherosclerosis), ophthalmology and anti-inflammatory agents. The company’s flagship product, LIVALO^® (pitavastatin), is approved in 46 countries around the world.

Kowa Pharmaceuticals America, Inc., headquartered in Montgomery, AL, is focused primarily in the area of cardiometabolic diseases. Established in September 2008, Kowa Pharmaceuticals America focuses its efforts on the successful commercialization of its current and near-term portfolio of pharmaceutical products, and business development activities. For more information about Kowa Pharmaceuticals America, visit www.kowapharma.com.

LIVALO^® is a registered trademark of the Kowa group of companies.

 

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